The overall objectives of this grant application are: 1. To establish a high-precision isotope ratio mass spectrometry facility for the measurement of respiratory 13 CO2 abundance in neonatal, pediatric and obstetric patients following the administration of C13-labeled substrates. These non-radioactive compounds are chosen for their possession of a target bond whose cleavage liberates a 13 CO2 producing functional group and whose rate or extent of metabolism to 13 CO2 can be used as non-invasive diagnostic measure of the presence or absence of disease. These techniques are being developed specifically to permit diagnosis and research in those populations where radioactive tracers are contra-indicated. The substrates which have been selected on the basis of their demonstrated utility as C14 labeled forms include triotanoin (for assessing pancreatic lipolytic function); glycoholic acid (bile acid malabsorption or bacterial overgrowth); lactose (milk intolerance or lactase deficiency) and aminopyrine (assessment of liver microsomal mass and drug-drug interactions). 2. To establish the baseline parameters of 13CO2 abundance ratios in normal and disease states, their relationship to endogenous substrate metabolism, physiological state and CO2 production, so as to predict the minimum excursion in 13CO2 abundance which will have reliable diagnostic significance. 3. To design, synthesize and test new substrates with target bonds that would permit in vivo measurement of other endogenous or foreign enzymatic processes, and to extend the use of such substrates to the assessment of pharmacological activity, optimum dosage and drug-drug interactions.